• 1.

    WHO , 2020. World Malaria Report 2020: 20 Years of Global Progress and Challenges. Geneva, Switzerland: World Health Organization, 299.

    • Search Google Scholar
    • Export Citation
  • 2.

    Salanti A et al.2004. Evidence for the involvement of VAR2CSA in pregnancy-associated malaria. J Exp Med 200: 11971203.

  • 3.

    Lennartz F et al.2017. Structure-guided identification of a family of dual receptor-binding PfEMP1 that is associated with cerebral malaria. Cell Host Microbe 21: 403414.

    • Search Google Scholar
    • Export Citation
  • 4.

    Hviid L, Jensen AT , 2015. PfEMP1—a parasite protein family of key importance in Plasmodium falciparum malaria immunity and pathogenesis. Adv Parasitol 88: 5184.

    • Search Google Scholar
    • Export Citation
  • 5.

    Taylor SM, Parobek CM, Fairhurst RM , 2012. Haemoglobinopathies and the clinical epidemiology of malaria: a systematic review and meta-analysis. Lancet Infect Dis 12: 457468.

    • Search Google Scholar
    • Export Citation
  • 6.

    Agarwal A et al.2000. Hemoglobin C associated with protection from severe malaria in the Dogon of Mali, a West African population with a low prevalence of hemoglobin S. Blood 96: 23582363.

    • Search Google Scholar
    • Export Citation
  • 7.

    Fairhurst RM et al.2005. Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria. Nature 435: 11171121.

  • 8.

    Kilian N, Srismith S, Dittmer M, Ouermi D, Bisseye C, Simpore J, Cyrklaff M, Sanchez CP, Lanzer M , 2015. Hemoglobin S and C affect protein export in Plasmodium falciparum-infected erythrocytes. Biol Open 4: 400410.

    • Search Google Scholar
    • Export Citation
  • 9.

    Huynh BT, Fievet N, Gbaguidi G, Dechavanne S, Borgella S, Guezo-Mevo B, Massougbodji A, Ndam NT, Deloron P, Cot M , 2011. Influence of the timing of malaria infection during pregnancy on birth weight and on maternal anemia in Benin. Am J Trop Med Hyg 85: 214220.

    • Search Google Scholar
    • Export Citation
  • 10.

    Tetard M, Milet J, Dechavanne S, Fievet N, Dorin-Semblat D, Elion J, Fairhurst RM, Deloron P, Tuikue-Ndam N, Gamain B , 2017. Heterozygous HbAC but not HbAS is associated with higher newborn birthweight among women with pregnancy-associated malaria. Sci Rep 7: 1414.

    • Search Google Scholar
    • Export Citation
  • 11.

    Cottrell G, Moussiliou A, Luty AJ, Cot M, Fievet N, Massougbodji A, Deloron P, Tuikue Ndam N , 2015. Submicroscopic Plasmodium falciparum infections are associated with maternal anemia, premature births, and low birth weight. Clin Infect Dis 60: 14811488.

    • Search Google Scholar
    • Export Citation
  • 12.

    Lopez-Perez M, Larsen MD, Bayarri-Olmos R, Ampomah P, Stevenson L, Arevalo-Herrera M, Herrera S, Hviid L , 2018. IgG responses to the Plasmodium falciparum antigen VAR2CSA in Colombia are restricted to pregnancy and are not induced by exposure to Plasmodium vivax. Infect Immun 86: e00136e18.

    • Search Google Scholar
    • Export Citation
  • 13.

    Stevenson L, Laursen E, Cowan GJ, Bandoh B, Barfod L, Cavanagh DR, Andersen GR, Hviid L , 2015. alpha2-macroglobulin can crosslink multiple Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) molecules and may facilitate adhesion of parasitized erythrocytes. PLoS Pathog 11: e1005022.

    • Search Google Scholar
    • Export Citation
  • 14.

    Olsen RW, Ecklu-Mensah G, Bengtsson A, Ofori MF, Kusi KA, Koram KA, Hviid L, Adams Y, Jensen ATR , 2019. Acquisition of IgG to ICAM-1-binding DBLbeta domains in the Plasmodium falciparum erythrocyte membrane protein 1 antigen family varies between groups A, B, and C. Infect Immun 87: e00224e19.

    • Search Google Scholar
    • Export Citation
  • 15.

    Theisen M, Vuust J, Gottschau A, Jepsen S, Hogh B , 1995. Antigenicity and immunogenicity of recombinant glutamate-rich protein of Plasmodium falciparum expressed in Escherichia coli. Clin Diagn Lab Immunol 2: 3034.

    • Search Google Scholar
    • Export Citation
  • 16.

    Lopez-Perez M, Viwami F, Seidu Z, Jensen ATR, Doritchamou J, Ndam N, Hviid L, 2021. PfEMP1-specific IgG reactivity among Beninese pregnant women with sickle cell trait. Open Forum Infect Dis 8: ofab527.

  • 17.

    Fried M, Duffy PE , 2002. Analysis of CSA-binding parasites and antiadhesion antibodies. Methods Mol Med 72: 555560.

  • 18.

    Fried M, Nosten F, Brockman A, Brabin BJ, Duffy PE , 1998. Maternal antibodies block malaria. Nature 395: 851852.

  • 19.

    Ricke CH, Staalsoe T, Koram K, Akanmori BD, Riley EM, Theander TG, Hviid L , 2000. Plasma antibodies from malaria-exposed pregnant women recognize variant surface antigens on Plasmodium falciparum–infected erythrocytes in a parity-dependent manner and block parasite adhesion to chondroitin sulfate A. J Immunol 165: 33093316.

    • Search Google Scholar
    • Export Citation
  • 20.

    Chauvet M et al.2019. Impact of hemoglobin S trait on cell surface antibody recognition of Plasmodium falciparum-infected erythrocytes in pregnancy-associated malaria. Open Forum Infect Dis 6: ofz156.

    • Search Google Scholar
    • Export Citation
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Natural Acquired Immunity to Malaria Antigens among Pregnant Women with Hemoglobin C Trait

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  • 1 Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
  • | 2 UMR 261 MERIT, Université de Paris, Institut de Recherche pour le Développement (IRD), Paris, France;
  • | 3 Institut de Recherche Clinique du Benin, Abomey Calavi, Benin;
  • | 4 Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana;
  • | 5 Centre for Medical Parasitology, Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark
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ABSTRACT.

Hemoglobin C is the second most common structural hemoglobinopathy in Africa, and carriers have a reduced risk of severe malaria. However, the effect of HbAC on the antibody response to malaria antigens in pregnancy has not been studied. Here, we measured PfEMP1-specific antibodies in plasma samples from 74 Beninese pregnant women with either HbAA or HbAC. IgG-mediated inhibition of VAR2CSA+ infected erythrocytes adhesion to chondroitin sulfate A (CSA) was also tested. PfEMP1-specific IgG levels to VAR2CSA were significantly lower in HbAC women, suggesting less exposure to VAR2CSA. In contrast, the percentage of VAR2CSA+-infected erythrocytes adhesion to CSA was not different between HbAA and HbAC women. Moreover, IgG levels to PfEMP1 variants associated with severe malaria were not significantly different between groups. The findings indicate similar exposure to Plasmodium falciparum parasites expressing PfEMP1 variants causing severe malaria, and justify more comprehensive studies of hemoglobinopathy-related qualitative and quantitative differences in PfEMP1-specific antibody responses.

Author Notes

Address correspondence to Mary Lopez-Perez, Panum Institute 07-11-38, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark. E-mail: mlopez@sund.ku.dk

Financial support: This work was funded by the Danish Council for Independent Research (grant 0134-00123B) to L. H. Sample collection in Benin was part of the STOPPAM collaborative project. N. T. N. was supported by the European 7th Framework Programme (grant 200889). J. D. was supported by a PhD studentship from Institut de Recherche pour le Développement.

Authors’ addresses: Mary Lopez-Perez and Lars Hviid, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark, E-mails: mlopez@sund.ku.dk and lhviid@sund.ku.dk. Firmine Viwami, UMR 261 MERIT, Université de Paris, Institut de Recherche pour le Développement (IRD), Paris, France, E-mail: vfeafr@yahoo.fr. Justin Doritchamou, Laboratory of Malaria Immunology & Vaccinology, National Institute of Allergy and Infectious Disease, National Institute of Health, Bethesda, MD, E-mail: yai.doritchamou@nih.gov. Nicaise Tuikue Ndam, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana, E-mail: nicaise.ndam@ird.fr.

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